PT - JOURNAL ARTICLE AU - Lino Becerra AU - Jaymin Upadhyay AU - Pei-Ching Chang AU - James Bishop AU - Julie Anderson AU - Richard Baumgartner AU - Adam J. Schwarz AU - Alexandre Coimbra AU - Diana Wallin AU - Lauren Nutile AU - Edward George AU - Gary Maier AU - Soujanya Sunkaraneni AU - Smriti Iyengar AU - Jeffrey L. Evelhoch AU - David Bleakman AU - Richard Hargreaves AU - David Borsook TI - Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy Human Subjects AID - 10.1124/jpet.112.201145 DP - 2013 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 41--51 VI - 345 IP - 1 4099 - http://jpet.aspetjournals.org/content/345/1/41.short 4100 - http://jpet.aspetjournals.org/content/345/1/41.full SO - J Pharmacol Exp Ther2013 Apr 01; 345 AB - Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug’s pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial µ-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.